Gastroesophageal cancers are the most rapidly increasing cancer in Caucasian males and are a consequence of Barrett's esophagus. Barrett's esophagus is a pre-malignant condition that is produced by gastroesophageal reflux disease (heartburn). Screening for Barrett's esophagus can only be accomplished by endoscopy that is expensive and impractical given the population at risk. The purpose of this proposal is to design an "optical biopsy" system that can be applied by a wide range of health care providers to screen for Barrett's esophagus. This system will consist of an optical probe that can be placed into the esophagus with minimal discomfort to the patient that is connected to an optical biopsy console that will provide real time results. The primary design issues will be in constructing a small caliber probe that can be comfortably placed into the esophagus and yet expandable to provide contact with the esophageal wall for an optical biopsy. The second design consideration would be in constructing an algorithm that would analyze the spectroscopic signal from the "optical biopsy" which would distinguish normal and abnormal tissue in the upper gastrointestinal tract. Three proposed probe designs will be evaluated initially in the resected porcine esophagus and stomach to assess deployment of the probes and their safety. Subsequently, the probes will be assessed in the pig model to evaluate their performance characteristics. The best design will be selected for clinical testing. The clinical trials will involve the use of the probe in patients with known Barrett's esophagus and a control group undergoing endoscopy for other indications. The probe would be passed prior to endoscopy and the results compared to the endoscopic findings. The algorithms will be derived from optical and histological biopsies taken simultaneously at endoscopy from patients undergoing surveillance endoscopy for Barrett's esophagus. The development of a screening device for Barrett's esophagus that could be operated by paramedical personnel would enable large-scale low cost screening to identify patients at risk for esophageal cancer.